The rapid advancement of nanotechnology has greatly expanded the range of biomaterials in biomedicine, including nanoparticles (NPs) made from conventional organic materials and inorganic biomaterials or organic/inorganic hybrid NPs. This expansion demonstrates the potential of engineered inorganic material-based NPs in therapeutics. Recent advances in nanomaterial-based therapeutics have allowed for imaging-guided biosafety and nanoimaging, opening up new possibilities in drug delivery and developing various therapeutic systems. With their distinctive properties, inorganic nanomaterials, such as carbon, metal, ceramic, and semiconductor-based nanomaterials, offer a promising future for therapeutic applications. However, ensuring the safe utilization of nanomaterials in clinical applications remains a significant concern. In this review, we have gathered recent research on the biosafety of nanomaterials in various therapeutic applications, both in vitro and in vivo. We have also discussed how size, surface functionalization, test species, and test conditions influence the formulation of particles and their biocompatibility. Furthermore, we have discussed the progress and challenges in developing nanoimaging nanomaterials for therapeutic purposes. In conclusion, with proper precautions and safe conditions, nanomaterials have excellent potential for future therapeutic applications, instilling optimism and hope for the future of medicine.